Renal disease in familial dysautonomia

Pearson, John; Gallo, Gloria; Gluck, Melvin C.; Axelrod, Felicia B.

doi:10.1038/ki.1980.12

Cited by 42 publications

(30 citation statements)

References 18 publications

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“…Many of the down-regulated genes participate in cell migration and survival, and this may explain neuropathological findings such as diminished numbers of small nerve fibers and neuronal loss in dorsal root ganglia [3]. The decrease in sympathetic neuronal innervation in FD seems to be pervasive, involving the skin [4], renal blood vessels [5], and the heart (unpublished observations).…”

Section: Hhs Public Accessmentioning

confidence: 99%

Plasma Catechols in Familial Dysautonomia: A Long-term Follow-up Study

2008

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This study tested whether familial dysautonomia (FD) involves progressive loss of noradrenergic nerves. Plasma levels of catechols, including dihydroxyphenylglycol (DHPG), norepinephrine (NE), dopamine (DA), and DOPA, were measured in 7 adult patients with FD and 50 healthy control subjects. FD patients were re-tested after a mean follow-up period of 13 years. Compared to controls, FD patients had low plasma levels of DHPG (P < 0.001), high DOPA and DA levels (P = 0.01, P = 0.0002), and high NE:DHPG (P < 0.0001), DA:NE (P = 0.0003), and DOPA:DHPG (P < 0.0001) ratios. At follow-up there were no changes in plasma levels of individual catechols; however, there were further increases in DOPA:DHPG ratios (mean 24 ± 7%, P = 0.01). In FD, plasma catechol profiles are sufficiently stable, at least over a decade, to be used as a biomarker of disease involvement. An increasing DOPA:DHPG ratio suggests slight but consistent, progressive loss of noradrenergic neurons.

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Section: Hhs Public Accessmentioning

confidence: 99%

Plasma Catechols in Familial Dysautonomia: A Long-term Follow-up Study

2008

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“…Previous studies described diminished sympathetic neuronal populations in biopsies of renal blood vessels and sural nerve [15,16], and decreased numbers of neurons in sympathetic ganglia harvested post-mortem. Note decreased radioactivity in FD at all time points, compared to untreated control subjects, with more rapid decline in radioactivity in the FD group compared to both untreated and desipramine-treated control subjects Consistent with decreased numbers of cardiac sympathetic neurons, at all time points after injection of the sympathetic neuroimaging agent (6-[ 18 F]fluorodopamine) myocardial concentrations of 6-[ 18 F]fluorodopamine-derived radioactivity were decreased by about 25% in the interventricular septum and about 30% in the left ventricular free wall, compared to values in untreated control subjects.…”

Section: Discussionmentioning

confidence: 97%

“…Post-mortem or biopsy studies have indicated that, rather than autonomic failure in FD reflecting dopamine-beta-hydroxylase deficiency, FD entails decreased numbers of sympathetic neurons. Blood vessels in renal and sural nerve biopsy tissue from FD patients have reduced sympathetic terminals [15,16], and sympathetic ganglia contain decreased numbers of neurons [17].…”

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confidence: 99%

Cardiac sympathetic hypo-innervation in familial dysautonomia

et al. 2008

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“…Renal insufficiency and need for dialysis are potential complications for the adult FD patient [18]. Patients were divided into those with or without evidence of renal insufficiency based on a serum creatinine of 2 mg% or greater.…”

Section: Assessing Long-term Effectsmentioning

confidence: 99%

Fludrocortisone in patients with familial dysautonomia

et al. 2005

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The common familial dysautonomia (FD) mutation causes a splicing defect that leads to production of both wild-type (WT) and mutant (MU) IKBKAP mRNA. Because drugs may alter splicing, seven drugs, fludrocortisone, midodrine, diazepam, albuterol, clonidine, caffeine, and dopamine were screened. Since only fludrocortisone negatively altered gene expression, we assessed fludrocortisone's efficacy in treating postural hypotension, and its effect on survival and secondary long-term FD problems. For 341 FD patients we obtained demographic data and clinical information from the last Center evaluation (most current or prior to death) including mean blood pressures (supine, 1 min erect and 5 min erect) and history regarding syncope and presyncope symptoms. For 175 fludrocortisone-treated patients, data from the evaluation prior to start of fludrocortisone and from the last Center evaluation were compared. The fludrocortisone-treated patient cohort was compared to the nontreated patient cohort with respect to overall survival and event-free survival for crisis frequency, worsening gait, frequent fractures, spine curvature, renal insufficiency, and pacemaker insertion. Overall survivals of patients on fludrocortisone alone, on fludrocortisone and midodrine, and on neither drug were compared. Cumulative survival was significantly higher in fludrocortisone-treated patients than in non-treated patients during the first decade. In subsequent decades, the addition of midodrine improved cumulative survival. Fludrocortisone significantly increased mean blood pressures and decreased dizziness and leg cramping, but not headaches or syncope. Fludrocortisone was associated with more long-term problems, which may reflect more symptomatic status associated with longer survival. Our data suggest that fludrocortisone has clinical efficacy despite negative in vitro observations on gene expression.

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Renal disease in familial dysautonomia

Cited by 42 publications

References 18 publications

Plasma Catechols in Familial Dysautonomia: A Long-term Follow-up Study

Plasma Catechols in Familial Dysautonomia: A Long-term Follow-up Study

Cardiac sympathetic hypo-innervation in familial dysautonomia

Fludrocortisone in patients with familial dysautonomia

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